Prostate Cancer
Conditions
Brief summary
The aim of the study is to determine if triptorelin formulated for use every 6 months (given twice during the study) is effective and safe for when given by injection under the skin for the treatment of adult males with cancer in the prostate.
Interventions
A prolonged release formulation of triptorelin pamoate 22.5 mg 6-month formulation in D, L-lactide-co-glycolide polymers for single subcutaneous injection on Day 1 and Day 169
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Participant is male and must be 18 years of age inclusive, at the time of signing the informed consent * Participant has histologically or cytologically proven prostate cancer with rising PSA after failed local therapy or metastatic disease, or requiring radiotherapy, and be a candidate for long-term (i.e. \>1 year) androgen deprivation therapy * Participant requires a GnRH analogue treatment for a minimum of 18 months, of which a minimum of 3 months of GnRH analogue treatment has already been provided prior to screening. (Note: participants must receive study intervention on Day 1 in accordance with the treatment schedule of their previously received GnRH analogue therapy). * Has serum testosterone levels \<1.735 nmol/L (50 ng/dL) at screening * Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 * Has a life expectancy of \>18 months * Male participants must agree that, if their partner is at risk of becoming pregnant (although highly unlikely in this study population), they will use an effective method of contraception. The participant must agree to use the contraception during the whole of the study and for 9 months after the last dose of study intervention * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
Exclusion criteria
: * Presence of another neoplastic lesion or brain metastases * Metastatic hormone-sensitive prostate cancer with high tumour burden * Metastatic castration-resistant prostate cancer * Any concomitant disorder or resulting therapy that is likely to interfere with participant compliance or with the study in the opinion of the investigator * Use of finasteride (Proscar®) or dutasteride (Avodart®/Avolve®) within the past 6 months * Planned intermittent scheme of GnRH analogue * At the time of screening, planned use of any chemotherapy for prostate cancer during the study * Prior hypophysectomy or adrenalectomy * Participation in another study with an experimental drug within 3 months before signing informed consent or within five half-lives of the investigational drug (whichever was the longer), or any other type of medical research * Severe kidney or liver failure (creatinine \>2 times the normal range, aspartate aminotransferase and alanine aminotransferase \>3 times the normal range) * Any concomitant disorder or resulting therapy that is likely to interfere with participant's compliance, the subcutaneous administration of the drug or with the study in the opinion of the investigator * Previous history of QT prolongation or concomitant use of medicinal products known to prolong the QT interval or with a known risk of torsades de pointes * Known hypersensitivity to triptorelin or any of its excipients, GnRH, other GnRH agonist/analogues * Known active use of recreational drug or alcohol dependence in the opinion of the investigator * Inability to give informed consent or to comply fully with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Maintained Castrate Levels of Serum Testosterone During the Study | Up to Day 337 | Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method. Maintenance of castration during the study was defined as testosterone \<1.735 nanomoles per liter (nmol/L) (\<50 nanograms/deciliter \[ng/dL\]) at Days 29, 85, 141, 169, 253, 309 and 337. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) During the Study | Up to Day 337 | Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method. |
| Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337 | Days 29, 85, 141, 169, 253, 309 and 337 | Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method. |
| Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337 | Days 29, 85, 141, 169, 253, 309 and 337 | Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method. Castration was defined as testosterone \<1.735 nmol/L (\<50 ng/dL). |
| Percent Change From Baseline in Prostate Specific Antigen (PSA) at Days 169 and 337 | Baseline (prior to injection on Day 1), Days 169 and 337 | Blood samples were collected for the measurement of plasma PSA concentrations. Percent change in PSA was defined as the absolute value of the difference between the PSA values at Days 169 and 337 and the baseline value divided by the baseline value. The baseline value was the last sample prior to the first injection. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs of Local Intolerance | From first dose of study treatment (Day 1) up to end of study visit (Day 337) | An adverse event (AE) was any untoward medical occurrence in clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. TEAEs were AEs that started or worsened on or after the first study treatment administration and within 168 days after the last dose of study treatment, or up to Day 337, whichever was later. Local tolerance was assessed 2 hours after each injection by examination of injection site for signs such as but not limited to tenderness, redness, bruising, erythema, swelling, rash, pain, itching, induration, hematoma, ulceration or necrosis. |
| Percentage of Participants Castrated on Days 3 and 7 After Each Injection Administered on Days 1 and 169 | On Days 3, 7, 171, and 175 | Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method. Castration was defined as testosterone \<1.735 nmol/L (\<50 ng/dL). |
Countries
Belgium, Czechia, France, Germany, Lithuania, Netherlands, Spain
Participant flow
Recruitment details
This Phase III, multicenter, open-label, single arm study was conducted at 26 investigational sites in 6 countries from 30-Aug-2022 to 08-Jul-2024 in participants with locally advanced and/or metastatic prostate cancer previously treated and castrated with a gonadotropin-releasing hormone (GnRH) analogue.
Pre-assignment details
The study consisted of a screening period (Day -28 to Day -1), study treatment administration on Days 1 and 169 (with visits on Days 3, 7, 29, 85, 141, 171, 175, 253, 309) and an end of study/early discontinuation visit on Day 337. A total of 147 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Triptorelin Embonate 22.5 mg Participants received triptorelin embonate 22.5 mg SC injection on Days 1 and 169. | 147 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Deviation | 3 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Triptorelin Embonate 22.5 mg |
|---|---|
| Age, Continuous | 71.8 years STANDARD_DEVIATION 8.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 39 Participants |
| Race/Ethnicity, Customized Not Reported | 36 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 109 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 147 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 145 |
| other Total, other adverse events | 38 / 145 |
| serious Total, serious adverse events | 26 / 145 |
Outcome results
Primary
Percentage of Participants Who Maintained Castrate Levels of Serum Testosterone During the Study
Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method. Maintenance of castration during the study was defined as testosterone \<1.735 nanomoles per liter (nmol/L) (\<50 nanograms/deciliter \[ng/dL\]) at Days 29, 85, 141, 169, 253, 309 and 337.
Time frame: Up to Day 337
Population: The full analysis set (FAS) included all participants who signed an informed consent form (ICF) and received 2 administrations of study treatment and completed all visits for testosterone measurement (Days 29, 85, 141, 169, 253, 309 and 337).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triptorelin Embonate 22.5 mg | Percentage of Participants Who Maintained Castrate Levels of Serum Testosterone During the Study | 95.0 percentage of participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs of Local Intolerance
An adverse event (AE) was any untoward medical occurrence in clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. TEAEs were AEs that started or worsened on or after the first study treatment administration and within 168 days after the last dose of study treatment, or up to Day 337, whichever was later. Local tolerance was assessed 2 hours after each injection by examination of injection site for signs such as but not limited to tenderness, redness, bruising, erythema, swelling, rash, pain, itching, induration, hematoma, ulceration or necrosis.
Time frame: From first dose of study treatment (Day 1) up to end of study visit (Day 337)
Population: The safety set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Triptorelin Embonate 22.5 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs of Local Intolerance | TEAEs | 88 Participants |
| Triptorelin Embonate 22.5 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs of Local Intolerance | TEAEs of Local Intolerance | 19 Participants |
Secondary
Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337
Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method. Castration was defined as testosterone \<1.735 nmol/L (\<50 ng/dL).
Time frame: Days 29, 85, 141, 169, 253, 309 and 337
Population: The FAS included all participants who signed an ICF and received 2 administrations of study treatment and completed all visits for testosterone measurement (Days 29, 85, 141, 169, 253, 309 and 337).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337 | Day 29 | 100.0 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337 | Day 85 | 100.0 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337 | Day 141 | 98.3 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337 | Day 169 | 97.5 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337 | Day 253 | 100.0 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337 | Day 309 | 99.2 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 29, 85, 141, 169, 253, 309 and 337 | Day 337 | 99.2 percentage of participants |
Secondary
Percentage of Participants Castrated on Days 3 and 7 After Each Injection Administered on Days 1 and 169
Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method. Castration was defined as testosterone \<1.735 nmol/L (\<50 ng/dL).
Time frame: On Days 3, 7, 171, and 175
Population: The FAS included all participants who signed an ICF and received 2 administrations of study treatment and completed all visits for testosterone measurement (Days 29, 85, 141, 169, 253, 309 and 337).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 3 and 7 After Each Injection Administered on Days 1 and 169 | Day 3 | 92.5 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 3 and 7 After Each Injection Administered on Days 1 and 169 | Day 7 | 98.3 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 3 and 7 After Each Injection Administered on Days 1 and 169 | Day 171 | 95.0 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants Castrated on Days 3 and 7 After Each Injection Administered on Days 1 and 169 | Day 175 | 95.8 percentage of participants |
Secondary
Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) During the Study
Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method.
Time frame: Up to Day 337
Population: The FAS included all participants who signed an ICF and received 2 administrations of study treatment and completed all visits for testosterone measurement (Days 29, 85, 141, 169, 253, 309 and 337).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triptorelin Embonate 22.5 mg | Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) During the Study | 83.3 percentage of participants |
Secondary
Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337
Blood samples were collected for the measurement of serum testosterone concentrations using a validated, specific and sensitive liquid chromatography tandem mass spectrometry method.
Time frame: Days 29, 85, 141, 169, 253, 309 and 337
Population: The FAS included all participants who signed an ICF and received 2 administrations of study treatment and completed all visits for testosterone measurement (Days 29, 85, 141, 169, 253, 309 and 337).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Triptorelin Embonate 22.5 mg | Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337 | Day 29 | 92.5 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337 | Day 85 | 92.5 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337 | Day 141 | 92.5 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337 | Day 169 | 94.2 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337 | Day 253 | 95.8 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337 | Day 309 | 95.8 percentage of participants |
| Triptorelin Embonate 22.5 mg | Percentage of Participants With a Serum Testosterone Level <0.694 Nmol/L (<20 ng/dL) on Days 29, 85, 141, 169, 253, 309 and 337 | Day 337 | 98.3 percentage of participants |
Secondary
Percent Change From Baseline in Prostate Specific Antigen (PSA) at Days 169 and 337
Blood samples were collected for the measurement of plasma PSA concentrations. Percent change in PSA was defined as the absolute value of the difference between the PSA values at Days 169 and 337 and the baseline value divided by the baseline value. The baseline value was the last sample prior to the first injection.
Time frame: Baseline (prior to injection on Day 1), Days 169 and 337
Population: The FAS included all participants who signed an ICF and received 2 administrations of study treatment and completed all visits for testosterone measurement (Days 29, 85, 141, 169, 253, 309 and 337). Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Triptorelin Embonate 22.5 mg | Percent Change From Baseline in Prostate Specific Antigen (PSA) at Days 169 and 337 | Day 169 | 0.00 percent change |
| Triptorelin Embonate 22.5 mg | Percent Change From Baseline in Prostate Specific Antigen (PSA) at Days 169 and 337 | Day 337 | 0.00 percent change |